Process for the resolution of racemic α-aminonitriles

Abstract

Process for the resolution of certain racemic α-aminonitriles into optically active enantiomers which includes treating the racemic α-aminonitriles with (-)-dibenzoyl-tartaric acid in polar solvents to obtain a racemic mixture of diastereoisomeric D and L salts of (-)-dibenzoyl-tartaric acid, macerating the salts with dioxane, neutralizing the L-form, extracting the neutralized product, and converting it into a stable form.

What is claimed is: 
     
       1. Process for the resolution of racemic α-aminonitriles of the general formula: ##STR4## wherein R 1  stands for a hydrogen atom or a methyl group, R 2  stands for a hydrogen atom or a methoxy group, and   R 3  stands for a hydrogen atom or a methyl group, into optically active enantiomers, which comprises: (A) treating said racemic α-aminonitriles with (-)-dibenzoyl-tartaric acid in organic polar solvent in order to thereby obtain a macemic mixture of diastereoisomeric D and L salts of (-)-dibenzoyl-tartaric acid;   (B) macerating said racemic mixture of diastereoisomeric D and L salts of (-)-dibenzoyl-tartaric acid with dioxane or water/dioxane mixture containing at least 85% by volume dioxane to thereby obtain D- and L-aminonitrile (-)-dibenzoyl-bitartrate;   (C) neutralizing the L-form;   (D) extracting the neutralized product obtained in step (C) above with a chlorinated aliphatic hydrocarbon; and   (E) converting said neutralized product to a hydrochloride or acetyl derivative.     
     
     
       2. Process as claimed in claim 1, characterized in that D-aminonitrile-(-)-dibenzoyl-bitartrate is racemized by means of ammonia and recycled. 
     
     
       3. The process of claim 1 wherein said polar solvent is selected from the group of alkanol, and acetone. 
     
     
       4. The process of claim 3 wherein said alkanol is selected from the group of methanol, ethanol, and isopropanol. 
     
     
       5. The process of claim 1 wherein said L-form is neutralized with ammonia. 
     
     
       6. The process of claim 1 wherein said chlorinated aliphatic hydrocarbon is chloroform. 
     
     
       7. The process of claim 1 wherein the macerization is performed at a temperature of 22° C. 
     
     
       8. The process of claim 7 wherein the treating with (-)-dibenzoyl-tartaric acid is performed at a temperature of about 0°-5° C. 
     
     
       9. The process of claim 1 wherein the treating with (-)-dibenzoyl-tartaric acid is performed at a temperature of about 0°-5° C. 
     
     
       10. The process of claim 1 wherein said water/dioxane mixture contains about 99% by volume of dioxane. 
     
     
       11. The process of claim 1 wherein said polar solvent is selected from the group of methanol, isopropanol, and acetone, said chlorinated aliphatic hydrocarbon is chloroform; the treating with (-)-dibenzoyl-tartaric acid is performed at about 0° to 5° C.; and the macerization is performed at a temperature of 22° C. 
     
     
       12. The process of claim 11 wherein said L-form is neutralized with ammonia. 
     
     
       13. The process of claim 1 wherein the racemic α-aminonitrile is D,L-amino-(3,4-dimethoxy-benzyl)-propionitrile. 
     
     
       14. The process of claim 1 wherein the salt of D-aminonitrile with (-)-mandelic acid is racemized in alkaline media into the corresponding D,L-aminonitrile and recycled to the process. 
     
     
       15. The process of claim 11 wherein the salt of D-aminonitrile with (-)-mandelic acid is racemized in alkaline media into the corresponding D,L-aminonitrile and recycled to the process. 
     
     
       16. The process of claim 1 wherein said organic polar solvent includes a ketone. 
     
     
       17. The process of claim 1 wherein said organic polar solvent includes an alkanol.